Effect of Remazolam on Intestinal Injury in Burn Sepsis Model Rats by Regulating the Notch-1/Hes Signaling Pathway
10.3969/j.issn.1671-7414.2025.02.028
- VernacularTitle:瑞马唑仑通过调节Notch-1/Hes信号通路对烧伤脓毒症模型大鼠肠道损伤的作用机制研究
- Author:
Huizhen WU
1
;
Jian PENG
1
;
Yanqiong XIA
1
Author Information
1. 武汉市第三医院麻醉科,武汉 430070
- Publication Type:Journal Article
- Keywords:
remazolam;
Notch-1/hairy and enhancer of split homolog signaling pathway;
burn sepsis;
intestinal injury
- From:
Journal of Modern Laboratory Medicine
2025;40(2):150-155
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of Remazolam(RZ)on intestinal injury in burn sepsis rats by regulating the Notch-1/hairy and enhancer of split homolog(Hes)signaling pathway.Methods Sixty SPF grade SD male rats were randomly separated into Normal group,Model group,low-dose RZ group(RZ-L group,3 mg/kg RZ),high-dose RZ group(RZ-H group,6 mg/kg RZ)and high-dose RZ+Notch-1 activator Jagged1 group(RZ-H+Jagged1 group,6 mg/kg RZ+0.67 mg/kg Jagged1),with 12 rats in each group.A burn sepsis model was prepared by establishing a 20%total surface area(TBSA)third-degree burn(burn)model on the back of rats,followed by injection of Pseudomonas aeruginosa.HE staining was applied to observe rat ileum tissue's pathological changes and assess intestinal mucosal damage score(Chiu's score).ELISA method was used to detect the levels of serum endotoxin,D-lactate,diamine oxidase(DAO),interleukin(IL-6),tumor necrosis factor-α(TNF-α)and myeloperoxidase(MPO)in rats.RT-qPCR method was applied to detect the expression of Notch-1 and Hes mRNA in rat ileum tissue,and Western Blot was used to detect the expression of Notch-1/Hes signaling pathway-related proteins in rat ileum tissue.Results Compared with the Normal group,the intestinal mucosal injury score(5.30±0.48 vs 1.00±0.52),serum endotoxin(135.69±16.24 pg/ml vs 62.48±3.23 pg/ml),D-lactate(1403.58±68.97 pg/ml vs 752.06±25.29 pg/ml)and DAO levels(137.55±12.37 pg/ml vs 58.52±4.43 pg/ml),ileal tissue IL-6(186.45±16.37 ng/ml vs 21.32±3.66 ng/ml),TNF-α(163.37±11.40 ng/ml vs 15.52±1.03 ng/ml)and MPO levels(8.94±0.92 U/ml vs 2.35±0.33 U/ml),Notch-1 mRNA(1.86±0.19 vs 1.00±0.10)and protein(0.79±0.08 vs 0.21±0.02),Hes-1 mRNA(2.13±0.21 vs 1.00±0.12)and protein(0.88±0.09,0.32±0.03)expression levels in the Model group were greatly increased,and the differences were statistically significant(t=14.294～47.368,all P<0.05).Compared with the Model group,the corresponding indicators of the RZ-L and RZ-H groups showed opposite changes,and the differences were statistically significant(tRZ-L=5.650～21.448,tRZ-H=4.435～42.403,all P<0.05).The Notch-1 activator Jagged1 weakened the therapeutic effect of RZ on intestinal injury in burn sepsis rats.Conclusion RZ may alleviate intestinal injury in burn sepsis model rats by inhibiting the Notch-1/Hes signaling pathway.
